Abstract

The aminosalicylate mesalazine (mesalamine) forms the mainstay of treatment in ulcerative colitis (UC), a disease for which many commercial modified-release products have been developed with the aim of providing targeted gastrointestinal release. The release profiles of five of these commercial formulations were evaluated in bicarbonate buffer using a novel dissolution model that mimics the dynamic conditions of the gastrointestinal tract. Monolithic and multi-particulate mesalazine formulations with pH-dependent and/or independent release mechanisms were evaluated (Asacol® 800, Octasa®, Mezavant® XL, Salofalk®, Pentasa®), and each of the products displayed a distinctive dissolution profile. The dissolution results for Mezavant® XL (Lialda®) (lag time 290 min) demonstrated good correlation with previously reported in vivo disintegration times assessed by gamma-scintigraphy in humans. Octasa® showed a similar lag time to Mezavant® XL. Drug release from Asacol® 800 (Asacol® HD) showed a wide standard deviation, reflecting the great variability in vivo. Salofalk® displayed both delayed release and extended release characteristics. Pentasa® released more than 50% of its drug load in the stomach compartment of the model, which is attributed to the absence of a gastro-resistant coating in this product. The new dissolution method provided a realistic and discriminative in vitro assessment of mesalazine release from different formulations. These results demonstrate that this strategy can be used to predict intestinal release behaviour, and potentially aid the rational design of products developed to target different sites of the gut.

abstract = "The aminosalicylate mesalazine (mesalamine) forms the mainstay of treatment in ulcerative colitis (UC), a disease for which many commercial modified-release products have been developed with the aim of providing targeted gastrointestinal release. The release profiles of five of these commercial formulations were evaluated in bicarbonate buffer using a novel dissolution model that mimics the dynamic conditions of the gastrointestinal tract. Monolithic and multi-particulate mesalazine formulations with pH-dependent and/or independent release mechanisms were evaluated (Asacol{\circledR} 800, Octasa{\circledR}, Mezavant{\circledR} XL, Salofalk{\circledR}, Pentasa{\circledR}), and each of the products displayed a distinctive dissolution profile. The dissolution results for Mezavant{\circledR} XL (Lialda{\circledR}) (lag time 290 min) demonstrated good correlation with previously reported in vivo disintegration times assessed by gamma-scintigraphy in humans. Octasa{\circledR} showed a similar lag time to Mezavant{\circledR} XL. Drug release from Asacol{\circledR} 800 (Asacol{\circledR} HD) showed a wide standard deviation, reflecting the great variability in vivo. Salofalk{\circledR} displayed both delayed release and extended release characteristics. Pentasa{\circledR} released more than 50{\%} of its drug load in the stomach compartment of the model, which is attributed to the absence of a gastro-resistant coating in this product. The new dissolution method provided a realistic and discriminative in vitro assessment of mesalazine release from different formulations. These results demonstrate that this strategy can be used to predict intestinal release behaviour, and potentially aid the rational design of products developed to target different sites of the gut.",

N2 - The aminosalicylate mesalazine (mesalamine) forms the mainstay of treatment in ulcerative colitis (UC), a disease for which many commercial modified-release products have been developed with the aim of providing targeted gastrointestinal release. The release profiles of five of these commercial formulations were evaluated in bicarbonate buffer using a novel dissolution model that mimics the dynamic conditions of the gastrointestinal tract. Monolithic and multi-particulate mesalazine formulations with pH-dependent and/or independent release mechanisms were evaluated (Asacol® 800, Octasa®, Mezavant® XL, Salofalk®, Pentasa®), and each of the products displayed a distinctive dissolution profile. The dissolution results for Mezavant® XL (Lialda®) (lag time 290 min) demonstrated good correlation with previously reported in vivo disintegration times assessed by gamma-scintigraphy in humans. Octasa® showed a similar lag time to Mezavant® XL. Drug release from Asacol® 800 (Asacol® HD) showed a wide standard deviation, reflecting the great variability in vivo. Salofalk® displayed both delayed release and extended release characteristics. Pentasa® released more than 50% of its drug load in the stomach compartment of the model, which is attributed to the absence of a gastro-resistant coating in this product. The new dissolution method provided a realistic and discriminative in vitro assessment of mesalazine release from different formulations. These results demonstrate that this strategy can be used to predict intestinal release behaviour, and potentially aid the rational design of products developed to target different sites of the gut.

AB - The aminosalicylate mesalazine (mesalamine) forms the mainstay of treatment in ulcerative colitis (UC), a disease for which many commercial modified-release products have been developed with the aim of providing targeted gastrointestinal release. The release profiles of five of these commercial formulations were evaluated in bicarbonate buffer using a novel dissolution model that mimics the dynamic conditions of the gastrointestinal tract. Monolithic and multi-particulate mesalazine formulations with pH-dependent and/or independent release mechanisms were evaluated (Asacol® 800, Octasa®, Mezavant® XL, Salofalk®, Pentasa®), and each of the products displayed a distinctive dissolution profile. The dissolution results for Mezavant® XL (Lialda®) (lag time 290 min) demonstrated good correlation with previously reported in vivo disintegration times assessed by gamma-scintigraphy in humans. Octasa® showed a similar lag time to Mezavant® XL. Drug release from Asacol® 800 (Asacol® HD) showed a wide standard deviation, reflecting the great variability in vivo. Salofalk® displayed both delayed release and extended release characteristics. Pentasa® released more than 50% of its drug load in the stomach compartment of the model, which is attributed to the absence of a gastro-resistant coating in this product. The new dissolution method provided a realistic and discriminative in vitro assessment of mesalazine release from different formulations. These results demonstrate that this strategy can be used to predict intestinal release behaviour, and potentially aid the rational design of products developed to target different sites of the gut.